The presence of genetic changes in the germ line that predispose to cancer, and the development of molecular diagnostic techniques that identify these changes, will make it possible to identify individuals in the population who are at higher risk of developing cancer. The identification of such individuals introduces the possibility of intervention to prevent the development of cancer or, if cancer does occur, to prevent it from causing death. The obvious scientific importance of this field, as well as the likely public demand for testing, identifies this area as a major target for investigation and development. However, before the scientific advances that make it possible to identify individuals predisposed to develop cancer can be translated into improved health for these individuals, a number of major scientific, clinical, epidemiological, ethical, and psycho-social questions must be answered. The long term goal of the work proposed in this application is to create a registry of families based on the population of the province of Ontario using rigorously defined methods of sampling. This registry will allow us to participate in collaborative research that will lead to an improved understanding of the contributions made to the etiology of breast cancer by environmental and genetic factors, to identify the factors responsible, and to gain an understanding of how they act, both separately and together, to influence risk of breast cancer. This information will be exploited in research into methods of preventing the disease. The specific goals of this proposal are: l. To collect pedigree information, epidemiologic data and related biological specimens from family members selected from the population of Ontario. We propose to meet this objective by using existing resources to assemble a population based series of family members at increased risk of breast cancer and a sample of members of families in which sporadic breast cancer has occurred to act as a non-familial comparison group for epidemiologic and other studies. 2. To identify a population at high risk for breast cancer that will participate in the evaluation of new preventive and therapeutic strategies. This population will be identified from the high risk families included in the registry as well as family members identified through the participating cancer centers and clinics.